Skip to main content
SpringerLink
Log in

Analysis of imprinted murine Peg3 locus in transgenic mice

  • Published:
Mammalian Genome Aims and scope Submit manuscript

Abstract

Peg3 is an imprinted gene exclusively expressed from the paternal allele. It encodes a C2H2 type zinc-finger protein and is involved in maternal behavior. It is important for TNF-NFkB signaling and p53-mediated apoptosis. To investigate the imprinting mechanism and gene expression of Peg3 and its neighboring gene(s), we used a 120 kb Peg3-containing BAC clone to generate transgenic mice. The BAC clone contains 20 kb of 5′ and 80 kb of 3′ flanking DNA, and we obtained three transgenic lines. In one of the lines harboring one copy of the transgene, Peg3 was imprinted properly. In the other two lines, Peg3 was expressed upon both maternal and paternal transmission. Imprinted expression was linked to the differential methylation of a region (DMR) upstream of the Peg3 gene. A second, maternally expressed gene, Zim1, present on the transgene was expressed irrespective of parental inheritance in all lines. These data suggest that, similar to other imprinted genes within domains, Peg3 and Zim1 are regulated by one or more elements lying at a distance from the genes. The imprinting of Peg3 seen in one line may reflect the presence of a responder sequence. Concerning the expression of the Peg3 transgene, we detected appropriate expression in the adult brain. However, this was not sufficient to rescue the maternal behavior phenotype seen in Peg3 deficient animals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. JF Ainscough T Koide M Tada S Barton MA Surani (1997) ArticleTitleImprinting of Igf2 and H19 from a 130 kb YAC transgene. Development 124 3621–3632

    Google Scholar 

  2. JF-X Ainscough RM John SC Barton MA Surani (2000) ArticleTitleA skeletal muscle-specific mouse Igf2 repressor lies 40 kb downstream of the gene. Development 127 3823–3830

    Google Scholar 

  3. AC Bell G Felsenfeld (2000) ArticleTitleMethylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405 482–485

    Google Scholar 

  4. Y Birger R Shemer J Perk A Razin (1999) ArticleTitleThe imprinting box of the mouse Igf2r gene. Nature 397 84–88

    Google Scholar 

  5. SM Blaydes M Elmore T Yang CI Brannan (1999) ArticleTitleAnalysis of murine Snrpn and human SNRPN gene imprinting in transgenic mice. Mamm Genome 10 549–555

    Google Scholar 

  6. JD Brenton RA Drewell S Viville KJ Hilton SC Barton et al. (1999) ArticleTitleA silencer element identified in Drosophila is required for imprinting of H19 reporter transgenes in mice. Proc Natl Acad Sci USA 96 9242–9247

    Google Scholar 

  7. K Buiting S Saitoh S Gross B Dittrich S Schwartz et al. (1995) ArticleTitleInherited microdeletions in the Angelman and Prader-Willi syndromes define an imprinting centre on human chromosome 15. Nat Genet 9 395–400

    Google Scholar 

  8. L Cai JF Taylor RA Wing DS Gallagher SS Woo et al. (1995) ArticleTitleConstruction and characterization of a bovine bacterial artificial chromosome library. Genomics 29 413–425

    Google Scholar 

  9. Y Deng X Wu (2000) ArticleTitlePeg3/Pw1 promotes p53-mediated apoptosis by inducing Bax translation from cytosol to mitochondria. Proc Natl Acad Sci USA 97 12050–12055

    Google Scholar 

  10. RA Drewell JD Brenton JF-X Ainscough SC Barton KJ Hilton et al. (2000) ArticleTitleDeletion of a silencer element disrupts H19 imprinting independently of a DNA methylation epigenetic switch. Development 127 3419–3428

    Google Scholar 

  11. GV Fitzpatrick PD Soloway MJ Higgins (2002) ArticleTitleThe brain on microarrays. Nat Genet 32 426–431 Occurrence Handle10.1038/ng988 Occurrence Handle1:CAS:528:DC%2BD38Xot1Klsbw%3D Occurrence Handle12410230

    Article  CAS  PubMed  Google Scholar 

  12. AT Hark CJ Schoenherr DJ Katz RS Ingram JM Levorse et al. (2000) ArticleTitleCTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405 486–489 Occurrence Handle10.1038/35013106 Occurrence Handle1:CAS:528:DC%2BD3cXjslykurY%3D Occurrence Handle10839547

    Article  CAS  PubMed  Google Scholar 

  13. RM John JF Ainscough SC Barton MA Surani (2001a) ArticleTitleDistant cis-elements regulate imprinted expression of the mouse p57(Kip2)/Cdkn1c gene: implications for the human disorder, Beckwith-Wiedemann Syndrome. Hum Mol Genet 10 1601–1609 Occurrence Handle10.1093/hmg/10.15.1601 Occurrence Handle1:CAS:528:DC%2BD3MXlvFOiur8%3D

    Article  CAS  Google Scholar 

  14. RM John SA Aparicio JF Ainscough KL Arney S Khosla et al. (2001b) ArticleTitleImprinted expression of neuronatin from modified BAC transgenes reveals regulation by distinct and distant enhancers. Dev Biol 236 387–399 Occurrence Handle10.1006/dbio.2001.0327 Occurrence Handle1:CAS:528:DC%2BD3MXlsVWgtrk%3D

    Article  CAS  Google Scholar 

  15. N Kikyo CM Williamson RM John SC Barton CV Beechey et al. (1997) ArticleTitleGenetic and functional analysis of neuronatin in mice with maternal or paternal duplication of distal Chr 2. Dev Biol 190 66–77 Occurrence Handle10.1006/dbio.1997.8681 Occurrence Handle1:CAS:528:DyaK2sXmvVertrs%3D Occurrence Handle9331332

    Article  CAS  PubMed  Google Scholar 

  16. J Kim X Lu L Stubbs (1999) ArticleTitle Zim1, a maternally expressed mouse Kruppel-type zinc-finger gene located in proximal chromosome 7. Hum Mol Genet 8 847–854 Occurrence Handle10.1093/hmg/8.5.847 Occurrence Handle1:CAS:528:DyaK1MXivFamtr0%3D Occurrence Handle10196374

    Article  CAS  PubMed  Google Scholar 

  17. J Kim VN Noskov X Lu A Bergmann X Ren et al. (2000) ArticleTitleDiscovery of a novel, paternally expressed ubiquitin-specific processing proteases gene through comparative analysis of an imprinted region of mouse chromosome 7 and human chromosome 19q13.4. Genome Res 10 1138–1147

    Google Scholar 

  18. J Kim A Kollhoff A Bergmann L Stubbs (2003) ArticleTitleMethylation-sensitive binding of transcription factor YY1 to an insulator sequence within the paternally expressed imprinted gene, Peg3. Hum Mol Genet 12 233–245 Occurrence Handle10.1093/hmg/ddg028 Occurrence Handle1:CAS:528:DC%2BD3sXitVWqtro%3D Occurrence Handle12554678

    Article  CAS  PubMed  Google Scholar 

  19. Y Kuroiwa T Kaneko-Ishino F Kagitani T Kohda LL Li et al. (1996) ArticleTitle Peg3 imprinted gene on proximal chromosome 7 encodes for a zinc finger protein. Nat Genet 12 186–190 Occurrence Handle1:CAS:528:DyaK28XosFCmug%3D%3D Occurrence Handle8563758

    CAS  PubMed  Google Scholar 

  20. L-L Li (1999) Characterisation and functional analysis of the imprinted Peg3 gene in mice. Ph.D. Thesis. University of Cambridge .

    Google Scholar 

  21. L Li EB Keverne SA Aparicio F Ishino SC Barton et al. (1999) ArticleTitleRegulation of maternal behavior and offspring growth by paternally expressed Peg3. Science 284 330–333 Occurrence Handle10.1126/science.284.5412.330 Occurrence Handle1:CAS:528:DyaK1MXitlOgt7Y%3D Occurrence Handle10195900

    Article  CAS  PubMed  Google Scholar 

  22. LL Li IY Szeto BM Cattanach F Ishino MA Surani (2000) ArticleTitleOrganization and parent-of-origin-specific methylation of imprinted Peg3 gene on mouse proximal chromosome 7. Genomics 63 333–340 Occurrence Handle10.1006/geno.1999.6103 Occurrence Handle1:CAS:528:DC%2BD3cXhsFShtrw%3D Occurrence Handle10704281

    Article  CAS  PubMed  Google Scholar 

  23. Y Obata T Kaneko-Ishino T Koide Y Takai T Ueda et al. (1998) ArticleTitleDisruption of primary imprinting during oocyte growth leads to the modified expression of imprinted genes during embryogenesis. Development 125 1553–1560 Occurrence Handle1:CAS:528:DyaK1cXjsVGntLc%3D Occurrence Handle9502736

    CAS  PubMed  Google Scholar 

  24. F Relaix X Weng G Marazzi E Yang N Copeland et al. (1996) ArticleTitle Pw1, a novel zinc finger gene implicated in the myogenic and neuronal lineages. Dev Biol 177 383–396 Occurrence Handle10.1006/dbio.1996.0172 Occurrence Handle1:CAS:528:DyaK28XkvVOks7o%3D Occurrence Handle8806818

    Article  CAS  PubMed  Google Scholar 

  25. F Relaix XJ Wei X Wu DA Sassoon (1998) ArticleTitle Peg3/Pw1 is an imprinted gene involved in the TNF-NFkappaB signal transduction pathway. Nat Genet 18 287–291 Occurrence Handle1:CAS:528:DyaK1cXhtlKqtLo%3D Occurrence Handle9500555

    CAS  PubMed  Google Scholar 

  26. F Relaix XJ Wei W Li J Pan Y Lin et al. (2000) ArticleTitlePw1/Peg3 is a potential cell death mediator and cooperates with Siah1a in p53-mediated apoptosis. Proc Natl Acad Sci USA 97 2105–2110 Occurrence Handle10.1073/pnas.040378897 Occurrence Handle1:CAS:528:DC%2BD3cXhslKhsbY%3D Occurrence Handle10681424

    Article  CAS  PubMed  Google Scholar 

  27. J Silva W Mak T Zvetkova R Appanah TB Nesterova et al. (2003) ArticleTitleEstablishment of histone H3 methylation on the inactive X chromosome requires transient recruitment of eed-enx1 polycomb group complexes. Dev Cell 4 481–495 Occurrence Handle10.1016/S1534-5807(03)00068-6 Occurrence Handle1:CAS:528:DC%2BD3sXjtFSmtLs%3D Occurrence Handle12689588

    Article  CAS  PubMed  Google Scholar 

  28. F Sleutels DP Barlow (2001) ArticleTitleInvestigation of elements sufficient to imprint the mouse Air promoter. Mol Cell Biol 21 5008–5017 Occurrence Handle10.1128/MCB.21.15.5008-5017.2001 Occurrence Handle1:CAS:528:DC%2BD3MXlsVGit7Y%3D Occurrence Handle11438657

    Article  CAS  PubMed  Google Scholar 

  29. F Sleutels R Zwart DP Barlow (2002) ArticleTitleThe non-coding Air RNA is required for silencing autosomal imprinted genes. Nature 415 810–813 Occurrence Handle1:CAS:528:DC%2BD38XhsFersrw%3D Occurrence Handle11845212

    CAS  PubMed  Google Scholar 

  30. JS Sutcliffe M Nakao S Christian KH Orstavik N Tommerup et al. (1994) ArticleTitleDeletion of a differentially methylated CpG island at the SNRPN gene defines a putative imprinting control region. Nat Genet 8 52–58 Occurrence Handle1:CAS:528:DyaK2cXmtVantrY%3D Occurrence Handle7987392

    CAS  PubMed  Google Scholar 

  31. IY Szeto LL Li MA Surani (2000) ArticleTitle Ocat, a paternally expressed gene closely linked and transcribed in the opposite direction to Peg3. Genomics 67 221–227 Occurrence Handle10.1006/geno.2000.6251 Occurrence Handle1:CAS:528:DC%2BD3cXkvFaku74%3D Occurrence Handle10903847

    Article  CAS  PubMed  Google Scholar 

  32. JL Thorvaldsen KL Duran MS Bartolomei (1998) ArticleTitleDeletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2. Genes Dev 12 3693–3702 Occurrence Handle1:CAS:528:DyaK1MXhtVamsA%3D%3D Occurrence Handle9851976

    CAS  PubMed  Google Scholar 

  33. A Ward R Fisher L Richardson J-A Pooler S Squire et al. (1997) ArticleTitleGenomic regions regulating imprinting and insulin-like growth factor-II promoter 3 activity in transgenics; novel enhancer and silencer elements. Genes Funct 1 25–36 Occurrence Handle1:CAS:528:DyaK2sXislGisro%3D Occurrence Handle9680326

    CAS  PubMed  Google Scholar 

  34. A Wutz OW Smrzka N Schweifer K Schellander EF Wagner et al. (1997) ArticleTitleImprinted expression of the Igf2r gene depends on an intronic CpG island. Nature 389 745–747 Occurrence Handle10.1038/39631 Occurrence Handle1:CAS:528:DyaK2sXmvVSns7c%3D Occurrence Handle9338788

    Article  CAS  PubMed  Google Scholar 

  35. A Yamaguchi M Taniguchi O Hori S Ogawa N Tojo et al. (2002) ArticleTitlePeg3/Pw1 is involved in p53-mediated cell death pathway in brain ischemia/hypoxia. J Biol Chem 277 623–629 Occurrence Handle10.1074/jbc.M107435200 Occurrence Handle1:CAS:528:DC%2BD38XjslGmsQ%3D%3D Occurrence Handle11679586

    Article  CAS  PubMed  Google Scholar 

  36. T Yang TE Adamson JL Resnick S Leff R Wevrick et al. (1998) ArticleTitleA mouse model for Prader-Willi syndrome imprinting-centre mutations. Nat Genet 19 25–31 Occurrence Handle1:CAS:528:DyaK1cXislWqurg%3D Occurrence Handle9590284

    CAS  PubMed  Google Scholar 

  37. JA Yeo EB Keverne (1986) ArticleTitleThe importance of vaginal-cervical stimulation for maternal behavior in the rat. Physiol Behav 37 23–26 Occurrence Handle10.1016/0031-9384(86)90378-1 Occurrence Handle1:STN:280:BimB1cjmsV0%3D Occurrence Handle3737720

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr. Rosalind John for critical reading of the manuscript, Kathy Hilton for technical assistance, and members of the Surani and McLaren laboratories for their support. I.Y.Y. Szeto was supported by a Cambridge Commonwealth Trust-Shell Scholarship

Author information

Authors and Affiliations

  1. Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology and Department of Physiology, University of Cambridge, Tennis Court Road, Cambridge, CB2, 1QR, UK

    Irene Y. Y. Szeto, Sheila C. Barton & Azim M. Surani

  2. Sub-department of Animal Behaviour, University of Cambridge, High Street, Madingley, Cambridge, CB3 8AA, UK

    E. B. Keverne

Authors
  1. Irene Y. Y. Szeto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheila C. Barton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. B. Keverne
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Azim M. Surani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Azim M. Surani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Szeto, I.Y., Barton, S.C., Keverne, E. et al. Analysis of imprinted murine Peg3 locus in transgenic mice . Mamm Genome 15, 284–295 (2004). https://doi.org/10.1007/s00335-003-3031-z

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-003-3031-z

Keywords

Search

Navigation